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The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome
Author(s) -
Habermann Jens K.,
Doering Jana,
Hautaniemi Sampsa,
Roblick Uwe J.,
Bündgen Nana K.,
Nicorici Daniel,
Kronenwett Ulrike,
Rathnagiriswaran Shruti,
Mettu Rama K. R.,
Ma Yan,
Krüger Stefan,
Bruch HansPeter,
Auer Gert,
Guo Nancy L.,
Ried Thomas
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24017
Subject(s) - breast cancer , gene expression profiling , genome instability , oncology , survival analysis , biology , gene expression , gene , gene signature , medicine , cancer , bioinformatics , genetics , dna , dna damage
Recently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the 2 groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets, such as luminal A and B, basal, normal‐like, and ERBB2+, and prognostic signatures including MammaPrint® and Oncotype DX, predicted genomic instability in our samples. This remarkable congruence suggests a biological interdependence of poor‐prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome. © 2008 Wiley‐Liss, Inc.